Legality of Compounded Estradiol for Embryo Transfer

The AABP office has received questions
from members regarding the legality of using compounded estradiol products in cattle
for embryo transfer protocols. AABP has also been in discussion with the FDA about
the use of compounded estradiol products in food animals. Compounding from approved
drugs in animals is only permitted under the narrowly defined conditions outlined
in AMDUCA (Section 21 CFR 530.13). To be permitted, extralabel use from compounding
of approved animal drugs or approved human drugs must be in compliance with all
relevant provisions of 21 CFR 530 (AMDUCA), including the provisions limiting extralabel
use to treatment modalities when the health of an animal is threatened or suffering
or death may result from failure to treat. The extralabel use regulation also does
not provide for compounding from active pharmaceutical ingredients (APIs or bulk
drugs—i.e., the raw chemical) for use in animals. Therefore, it is illegal for veterinarians
to use or prescribe compounded estradiol for cattle, or any form of estrogenic compounds
for production purposes, including embryo transfer and synchronization protocols.
AABP encourages cattle veterinarians to refrain from administering or prescribing
compounded estradiol for the following reasons:

AMDUCA only allows for
extralabel drug use when the health of an animal is threatened. There is no production
allowance, particularly for compounding; therefore one cannot use human-approved
drugs (e.g., ECP, Pfizer) or a different form of an animal-approved drug (e.g.,
growth-promoting implants) for production purposes.

Compounding from a bulk
product is specifically prohibited in AMDUCA regulations.

The safety, potency, efficacy,
stability, sterility, and disposition of compounded products is unknown. Compounded
products do not undergo FDA inspection, potency testing, or efficacy testing. Veterinary
compounding pharmacies that also compound for humans are under federal regulation
and are FDA inspected; however, this only applies to the human side of the compounding
operation. Veterinary compounding pharmacies do not have this level of oversight.
There is no guarantee of the safety or efficacy of compounded products, and liability
for the use of such products falls on the veterinarian in the event of an adverse
reaction or violative residue.

Because the safety, efficacy,
potency, and disposition of the compounded product is not known, it is impossible
to assign a withdrawal interval for compounded products.

The use of compounded products
in food animals places a veterinarian at risk of professional liability.

The need for estradiol for successful
embryo transfer protocols has not been unequivocally established. For example, data
from nearly 7,000 collections did not demonstrate a difference when using GnRH in
place of estradiol in the protocol.1 Additional references are available
on the Reproduction Committee page of the website at https://aabp.org/members/Reproduction.asp. Veterinarians who engage in federally prohibited activities
put themselves at risk and also risk the profession’s reputation for appropriate
and judicious oversight of pharmaceutical products in our cattle patients. This
is especially of concern when using an unapproved and illegally manufactured hormone
product.